There has been only a limited use for natural amphiphilic lipid excipients in pharmaceutical and cosmetic manufacture. The reasons are in many cases lack of raw material and high production costs, as well as poor performance of the final lipid material.
Among the natural polar, bilayer-forming lipids, i.e. amphiphilic lipids, the phospholipids are the most common in pharmaceutical and cosmetical use. Due to their bilayer-forming ability these polar lipids may be used for the formation of different kinds of aggregates and particles, such as vesicles and liquid crystals, which have found many technical applications.
However, there has only been a limited use of lipid gels based on phospholipids in pharmaceutical technology, mainly due to insufficient gel-forming abilities and poor chemical stability. The predominant natural polar, bilayer-forming lipid used so far, phosphatidylcholine from egg yolk or soybean, is slightly too lipophilic for optimal swelling in water and formation of the flexible bilayers which build up the liquid crystalline lamellar structures.
Since liposomes are dispersions of bilayer or lamellar phases in excess aqueous solution, it is thus not optimal to use phospholipid-based lamellar phases when forming liposomes. The swelling procedure is slow and a high input of mechanical energy is often required in order to form liposomes and vesicles from a phospholipid material within a reasonable period of time.
Natural phospholipids, such as phosphatidylcholine from egg yolk, are highly unsaturated. Unsaturation of the acyl chains of the phospholipid is a prerequisite for the formation of a liquid crystalline lamellar phase at room temperature. However, this also means that bilayer membranes formed by natural phospholipids possess a high permeability towards water-soluble drugs, since the acyl chains are in a disordered, fluid state. Liposomes made of natural phospholipids are thus characterised by a low encapsulation efficiency due to the leakage of incorporated drug across the liposomal bilayers. Normally, if drugs are to be incorporated into natural phospholipid liposomes, they must be stabilised by the addition of large amounts of cholesterol, 30-50 mole % of the total lipid composition.
This also applies to active substances other than drugs which for some reason are to be incorporated into liposomes or other bilayer structures.
Phospholipid-based vesicles and liposomes usually have a very short life-time after being introduced into circulation in the bloodstream. The rapid clearance from the blood is due to their uptake by the reticulo-endothelial system (RES) of the liver and the spleen. In order to overcome this, liposomes may be sterically stabilised by the addition of gangliosides, containing several carbohydrate units, or hydrophilic polymers, such as polyethylene oxide or pullulan. The latter agents are normally covalently bonded to phosphatidylethanolamine. In principle, this approach is very efficient and the modified liposomes may escape uptake by RES. In practice, it is however disadvantageous to add additional components, either natural and rare, and therefore expensive, or synthetic, and therefore not necessarily biocompatible, to the liposomal formulation, both from a safety and an economical point of view.